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miR-32-5p-mediated Dusp5 downregulation contributes to neuropathic pain

Journal Article · · Biochemical and Biophysical Research Communications
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  1. Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003 (China)
  2. Department of Spine Surgery, Taizhou First People's Hospital, Taizhou 318020 (China)

Highlights: • SNL enhanced miR-32-5p expression. • Downregulation of miR-32-5p suppressed neuropathic pain development in vivo. • miR-32-5p promoted inflammatory cytokines levels in microglial cells in vitro. • Dusp5 is a target gene of miR-32-5p. • The effect of miR-32-5p on neuropathic pain is reversed by Dusp5. Previous studies have demonstrated that microRNAs (miRNAs) play important roles in the pathogenesis of neuropathic pain. In the present study, we found that miR-32-5p was significantly upregulated in rats after spinal nerve ligation (SNL), specifically in the spinal microglia of rats with SNL. Functional assays showed that knockdown of miR-32-5p greatly suppressed mechanical allodynia and heat hyperalgesia, and decreased inflammatory cytokine (IL-1β, TNF-α and IL-6) protein expression in rats after SNL. Similarly, miR-32-5p knockdown alleviated cytokine production in lipopolysaccharide (LPS)-treated spinal microglial cells, whereas its overexpression had the opposite effect. Mechanistic investigations revealed Dual-specificity phosphatase 5 (Dusp5) as a direct target of miR-32-5p, which is involved in the miR-32-5p-mediated effects on neuropathic pain and neuroinflammation. We demonstrated for the first time that miR-32-5p promotes neuroinflammation and neuropathic pain development through regulation of Dusp5. Our findings highlight a novel contribution of miR-32-5p to the process of neuropathic pain, and suggest possibilities for the development of novel therapeutic options for neuropathic pain.

OSTI ID:
23134498
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN BBRCA9; ISSN 0006-291X
Country of Publication:
United States
Language:
English